The present invention relates to prostaglandin B.sub.1 derivatives, and more particularly to methods of preparing the prostaglandin B.sub.1 derivatives, PGB.sub.x, having the ability of restoring oxidative phosphorylation in aged degraded mitochondria.
A new class of polymeric derivatives PGB.sub.x of prostaglandin B.sub.1 (PGB.sub.1), called PGB.sub.x, and methods for preparation thereof are disclosed in U.S. Pat. Application Ser. No. 635,947 filed Nov. 28, 1975 by B. David Polis et al, now U.S. Pat. No. 4,153,808 issued May 8, 1979. The PGB.sub.x has the unique property of restoring the in vitro phosphorylating ability of degraded rat liver mitochrondria. Subsequent experiments have shown PGB.sub.x to have unique properties of reversing the degenerative effects of experimentally induced myocardial ischemia in monkeys and brain ischemia in rabbits. See Angelakos, E. T. et al, Recovery of Monkeys from Cardiogenic Shock after Myocardial Infarction with Ventricular Fibrillation-Effects of PGB.sub.x, Naval Air Development Center Report NADC-77308-60A, NTIS Accession No. AD A051744 (April 1978); and Kolata, R. J., The Effect of PGB.sub.x on Neurological Recovery from Cerebral Ischemia in Rabbits, Masters Thesis, University of Pennsylvania Veterinary School (1977).
Methods of the prior art for synthesizing, purifying, and assaying PGB.sub.x usually require a relatively long refluxing or heating process, and produced a relatively low yield of PGB.sub.x per unit weight of precursor. For example, the minimum preparation time for the methods disclosed in Patent Application Ser. No. 635,947 supra is 22 hours with a precursor of 13-14 dehydro PGB.sub.1. For the precursors of PGB.sub.1 and 13-14 dehydro PGB.sub.1, the yields of useful PGB.sub.x are 72% and 57%, respectively, and are of nonuniform biological activity.